crossing96/oncoscreening huggingface dataset:
ctDNA-Guided Adjuvant Atezolizumab in Muscle-Invasive Bladder Cancer.	BACKGROUND: Patients with muscle-invasive bladder cancer have varied outcomes after cystectomy. Circulating tumor DNA (ctDNA)-based detection of molecular residual disease may identify patients at high risk for recurrence after cystectomy who can benefit from adjuvant immunotherapy, thus sparing patients at lower risk from unnecessary treatment burden. METHODS: In a phase 3, double-blind, randomized trial, we used serial ctDNA testing to monitor (for up to 1 year) patients with muscle-invasive bladder cancer and no radiographic evidence of disease after surgery. Eligible patients who tested ctDNA-positive during surveillance were randomly assigned in a 2:1 ratio to receive intravenous atezolizumab or placebo every 4 weeks for up to 1 year. The primary end point was investigator-assessed disease-free survival. Overall survival was a secondary end point that was assessed in a hierarchical fashion to control for alpha. Patients who persistently tested ctDNA-negative did not receive atezolizumab or placebo. RESULTS: A total of 761 patients were enrolled; 250 eligible patients who tested ctDNA-positive underwent randomization (167 to the atezolizumab group and 83 to the placebo group). The median disease-free survival was 9.9 months with atezolizumab, as compared with 4.8 months with placebo (hazard ratio for first event of disease recurrence or death, 0.64; 95% confidence interval [CI], 0.47 to 0.87; P = 0.005). The median overall survival was 32.8 months with atezolizumab, as compared with 21.1 months with placebo (hazard ratio for death, 0.59; 95% CI, 0.39 to 0.90; P = 0.01). A total of 28% of the patients who received atezolizumab and 22% of those who received placebo had adverse events of grade 3 or 4 (related to atezolizumab or placebo in 7% vs. 4%); 3% and 2% of the patients, respectively, had fatal adverse events (related to atezolizumab or placebo in 2% vs. none). Among 357 patients with persistent ctDNA-negative status, disease-free survival was 95% at the end of the 1-year monitoring period and 88% at 2 years. CONCLUSIONS: Among patients with muscle-invasive bladder cancer, ctDNA-guided adjuvant therapy with atezolizumab led to significantly longer disease-free survival and overall survival than placebo. (Funded by F. Hoffmann-La Roche; IMvigor011 ClinicalTrials.gov number, NCT04660344.).	bladder
The Urinary Microbiota and the Gut-Bladder Axis in Bladder Cancer.	The human bladder hosts a resident, low-biomass microbial community (urobiota) that has only become the subject of intense investigation in the last 15 years. The advantages that the urobiota may confer to the bladder, in contrast to the microbiota of other mucosal sites, remain to be elucidated. Alterations in the urobiota have been associated with various pathological urogenital conditions, including urinary tract infections (UTIs) and recurrent UTIs. A potential link between bladder cancer (BC), the ninth most common human cancer by incidence worldwide, and a dysbiotic urobiota is still unclear and represents an emerging field of study. In this review, we focus on recent studies that not only analyzed the urobiota of BC patients using urine specimens to identify biomarkers and microbial signatures of the disease, but also monitored therapeutic responses to therapies. We also discuss novel techniques of culturing, such as culturomics, animal models of BC, and 3D organotypic models. Furthermore, we review studies on the gut-bladder axis which, though still limited, already suggest that diet- and gut-derived bacterial metabolites can influence BC progression and individual responses to therapy.	bladder
Overcoming immunotherapy resistance in bladder cancer with a novel antibody-drug conjugate RC48.	BACKGROUND: Immune checkpoint inhibitors have shown limited response rates in bladder cancer. RC48-antibody-drug conjugate (ADC) shows potential for combination with immune checkpoint inhibitors. This study aimed to elucidate RC48-ADC's mechanism in sensitizing tumors to immunotherapy and identify optimal combination strategies. METHODS: Bioinformatics (The Cancer Genome Atlas, GEO, Xiangya cohorts) analyzed correlations between HER2, immune markers, and therapy response. The h-HER2-MB49 and sg-PD-L1-MB49 cell line was generated. In vitro/vivo models assessed RC48-ADC's impact on the tumor immune microenvironment using flow cytometry, immunofluorescence, co-culture, chemotaxis, CUT&Tag assays, transcriptomics, and ELISA. Subcutaneous tumor models evaluated combination therapies. At the clinical level, bladder cancer immune therapy cohort tissue microarrays were used, and the aforementioned mechanisms were validated using immunohistochemistry and immunofluorescence. RESULTS: HER2 expression is associated with an inhibitory tumor immune microenvironment and resistance to immunotherapy. RC48-ADC treatment can reactivate this HER2-related inhibitory tumor immune microenvironment, thereby enhancing immunotherapy effectiveness. Mechanistically, RC48-ADC reactivates the tumor immune microenvironment by reducing PD-L1 transcription via Hippo pathway activation. It also promotes the release of chemokines (CCL5, CXCL9, and CXCL14) and recruits cytotoxic T-lymphocytes. In preclinical mouse models, RC48-ADC synergized with CTLA-4 and PD-L1 antibodies. CONCLUSIONS: RC48-ADC enhances immunotherapy by regulating PD-L1 through the Hippo-TAZ pathway and reactivating CD8+T cells, offering a novel combination therapeutic strategy for bladder cancer.	bladder
Metabolite-mediated mechanisms linking the urinary microbiome to bladder cancer.	Bladder cancer is the most common malignancy of the urinary tract and is a major health burden globally. Recent advances in microbiome research have revealed that the urinary tract harbors a resident microbial community, overturning the long-held belief in its sterility. Increasing evidence suggests that microbial dysbiosis and microbially derived metabolites contribute to bladder cancer carcinogenesis, progression, and therapeutic responses. Distinct microbial signatures have been observed in bladder cancer patients, with notable differences across disease stages and between primary and recurrent cases. Mechanistic studies have demonstrated that microbe-associated metabolites and toxins can drive DNA damage, chronic inflammation, extracellular matrix remodeling, and epithelial-mesenchymal transition. In addition, biofilm formation allows bacteria to evade immune responses and promotes persistent inflammation, creating a tumor-permissive niche. Beyond pathogenesis, microbial activity also influences therapeutic outcomes; for instance, some microbial pathways can inactivate frontline chemotherapy, while others generate metabolites with anti-tumor properties. Collectively, these patterns define a microbiota-metabolite-immunity axis, presenting opportunities for precision oncology. Targeting microbial pathways, profiling urinary microbiota, and harnessing beneficial metabolites offer promising advancements in biomarker discovery, prognostic refinement, and the development of novel therapeutic strategies for bladder cancer.	bladder
Cancer-associated fibroblast derived CXCL14 drives cisplatin chemoresistance by enhancing nucleotide excision repair in bladder cancer.	BACKGROUND: A significant challenge in bladder cancer treatment is primary chemoresistance, in which cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) play a pivotal role. While the contributions of CAFs to tumor progression and drug resistance are well established, the precise molecular mechanisms by which they induce chemoresistance remain unclear. A comprehensive understanding of the effect of TME modulation-particularly through CAFs-on the chemotherapeutic response is crucial for developing effective strategies to overcome chemoresistance and improve patient survival. METHODS: Primary fibroblasts were isolated from paired clinical samples of bladder cancer tissues and adjacent normal tissues to identify key CAF-derived secretory factors. Bioinformatics analysis, semiquantitative RT‒qPCR, and dual-luciferase reporter assays were subsequently used to investigate the functional role and mechanistic basis of CXCL14 in chemoresistance. The therapeutic relevance of these findings was further evaluated through in vitro and in vivo models, including ex vivo patient-derived organoid (PDO) models, by assessing cisplatin sensitivity and validating therapeutic targeting of the CXCL14-CCR7-STAT3 axis with small molecule inhibitors. RESULTS: Compared to normal fibroblasts and CAFs from nonchemoresistance groups, CAFs derived from cisplatin-resistant patients demonstrated significantly greater paracrine-mediated induction of chemoresistance. Mechanistically, CAF-secreted CXCL14 engaged CCR7 on bladder cancer cells, triggering STAT3 phosphorylation and consequently upregulating the DNA repair gene ERCC4 to promote cisplatin resistance. In vivo validation confirmed that pharmacological CCR7 or STAT3 inhibition markedly reversed chemoresistance and potentiated cisplatin-induced tumor cell death. Notably, STAT3 activation mediated the overexpression of the glycolytic enzymes HK2 and LDHA, resulting in greater glycolytic flux in resistant cells. This metabolic reprogramming further facilitated the transdifferentiation of normal fibroblasts into CXCL14-secreting CAFs, establishing a self-reinforcing feedback loop that sustains chemoresistance. CONCLUSION: The CXCL14/CCR7/STAT3 axis critically mediates cisplatin resistance in bladder cancer through dual modulation of DNA repair and glycolytic metabolism. Therapeutic cotargeting of this pathway with CCR7 or STAT3 inhibitors combined with cisplatin represents a promising strategy to overcome chemoresistance and improve clinical outcomes.	bladder
Durvalumab in combination with BCG for BCG-naive, high-risk, non-muscle-invasive bladder cancer (POTOMAC): final analysis of a randomised, open-label, phase 3 trial.	BACKGROUND: Patients with high-risk non-muscle-invasive bladder cancer (NMIBC) often have recurrence or progression after transurethral resection of bladder tumour (TURBT) and subsequent BCG therapy. We aimed to evaluate whether 1 year of durvalumab with BCG could improve outcomes versus BCG alone for these patients. METHODS: This randomised, open-label, phase 3 trial enrolled patients aged 18 years or older with BCG-naive, high-risk NMIBC who underwent TURBT. Patients were randomly allocated (1:1:1) to receive intravenous durvalumab (every 4 weeks for 13 cycles) plus intravesical BCG induction (weekly for 6 weeks) and maintenance (three doses at weekly intervals at 3, 6, 12, 18, and 24 months), durvalumab plus BCG induction, or BCG induction and maintenance (comparison group). The primary endpoint was investigator-assessed disease-free survival in the durvalumab plus BCG induction and maintenance group versus the comparison group in the intention-to-treat population. This study is registered at ClinicalTrials.gov (NCT03528694) and EudraCT (2017-002979-26) and is ongoing but is no longer enrolling patients. FINDINGS: Between June 18, 2018, and Oct 2, 2020, 1350 patients were assessed for eligibility, among whom 1018 patients were randomly allocated: 339 to the durvalumab plus BCG induction and maintenance group (of whom 336 [99%] initiated and 180 [53%] completed treatment), 339 to the durvalumab plus BCG induction group (337 [99%] initiated and 239 [71%] completed treatment), and 340 to the comparison group (339 [>99%] initiated and 182 [54%] completed treatment). At a median follow-up of 60·7 months (IQR 51·5-66·5), there were 67 (20%) disease-free survival events in the durvalumab plus BCG induction and maintenance group and 98 (29%) events in the comparison group, resulting in a 32% reduction in the risk of recurrence of high-risk disease or death by any cause with durvalumab plus BCG induction and maintenance versus the comparison group (hazard ratio 0·68 [95% CI 0·50-0·93]; log-rank p=0·015). Among patients who received at least one dose of study treatment, grade 3 or 4 treatment-related adverse events occurred in 71 (21%) of 336 patients in the durvalumab plus BCG induction and maintenance group, 52 (15%) in the durvalumab plus BCG induction only group, and 13 (4%) of 339 patients in the comparison group. No treatment-related adverse events led to death. INTERPRETATION: Among patients with BCG-naive, high-risk NMIBC, 1 year of durvalumab combined with BCG induction and maintenance therapy showed a statistically significant and clinically meaningful improvement in disease-free survival versus BCG induction and maintenance alone. The combination had a manageable safety profile, consistent with that of the individual therapies. These results support 1 year of durvalumab in combination with BCG induction and maintenance therapy as a potential new treatment for this patient population. FUNDING: AstraZeneca.	bladder
Neuroendocrine tumours of the urinary bladder: recent advances.	Small cell carcinoma is the most frequently encountered neuroendocrine tumour (NET) of the urinary bladder, and it may present as either pure or in combination with urothelial carcinoma or other histological subtypes. Large cell neuroendocrine carcinoma is increasingly recognized in this location, but it is not yet fully characterized. Well-differentiated NET and paraganglioma of the bladder are rare neuroendocrine neoplasms. Advances in the molecular characterization of these tumours have enhanced our understanding of their biology and can provide better classification and more accurate risk stratification for clinical decision-making.	bladder
Dynamic changes of urinary microbiota in patients with bladder cancer after surgery and its clinical significance.	Bladder cancer is one of the most common malignancies of the urogenital system, with a high incidence and mortality. The treatment of bladder cancer is diverse, with surgical treatment being the most common approach, including transurethral resection of bladder tumor and radical cystectomy. Following radical cystectomy, patients often undergo ileal neobladder reconstruction to restore urinary storage and voiding functions. However, postoperative changes in the urinary microbiota have become a major issue for bladder cancer patients. Traditionally, urine was believed to be sterile, but an increasing body of research has demonstrated the presence of a resident microbiota in urine, which is closely associated with the development of bladder diseases, postoperative complications, and patient prognosis. Dynamic changes in the urinary microbiota may lead to urinary tract infections, tumor recurrence, and other issues, severely affecting patients' recovery and quality of life. In recent years, with the advancement of high-throughput sequencing technology, research on the urinary microbiota has deepened, particularly regarding its changes and clinical significance after bladder cancer surgery. Although studies have explored the impact of urinary microbiota on recurrence and prognosis after bladder cancer surgery, research on urinary microbiota changes following ileal neobladder reconstruction is still limited. Therefore, this review aims to summarize the latest research on the dynamic changes of urinary microbiota in bladder cancer patients postoperatively, especially focusing on changes after ileal neobladder reconstruction, providing references for clinical treatment and future research directions.	bladder
Molecular pathology of bladder cancer.	Significant progress has been achieved in elucidating the molecular underpinnings of bladder cancer initiation and progression. Translational research has identified mutations in chromatin-modifying genes such as KMT2D and KDM6A, which facilitate colonization of larger regions of the urothelium. Subsequent mutations in TP53, PIK3CA, FGFR3 or RB1 drive malignant transformation. Advances in personalized oncology now integrate clinical, pathological and molecular classifications in bladder cancer, representing a paradigm shift in the management of locally advanced and metastatic disease. Alterations in FGFR3, commonly found in the luminal-papillary molecular subtype associated with low response to immunotherapy, are the target of erdafitinib. Enfortumab vedotin, which targets Nectin-4 (expressed in >95% of urothelial carcinomas), is approved for patients who progress after chemotherapy and/or immunotherapy. Evidence suggests that Nectin-4 gene amplification may further refine patient stratification. Sacituzumab govitecan, an antibody-drug conjugate directed against Trop-2, is effective in basal, luminal and stroma-rich subtypes but not in neuroendocrine carcinomas. In addition, therapies developed for HER2-positive breast cancer have shown efficacy in urothelial carcinoma, with recent data from the DESTINY pan-tumour phase II trial leading to FDA approval of trastuzumab deruxtecan for HER2-overexpressing metastatic urothelial carcinoma. This paper is a comprehensive review of the molecular pathology of bladder cancer, highlighting advances in molecular classification, biomarkers and personalized therapies. The transition from morphology-based classifications to combined morphological and molecular approaches, with therapeutic implications, is also addressed.	bladder
Contemporary management of metastatic urothelial carcinoma.	Urothelial carcinoma, the most common malignancy of the urinary tract, presents a significant challenge, particularly in its metastatic stage, where prognosis remains poor despite advancements in treatment. Historically, platinum-based chemotherapy has been the standard first-line therapy, achieving moderate response rates but limited long-term survival. Recent breakthroughs have introduced immune checkpoint inhibitors, antibody-drug conjugates (ADCs), and targeted therapies as more effective alternatives. Enfortumab vedotin plus pembrolizumab has demonstrated superior efficacy as a first-line treatment, improving overall survival (OS) and objective response rates compared to chemotherapy. Maintenance therapy with avelumab has further prolonged survival in patients responding to initial platinum-based chemotherapy. Additionally, sacituzumab govitecan, an ADC targeting Trop-2, and erdafitinib, a fibroblast growth factor receptor (FGFR) inhibitor, have provided promising options for patients with refractory disease or FGFR alterations. The evolving treatment paradigm now prioritizes biomarker-driven, personalized approaches over traditional chemotherapy-based regimens. However, challenges remain in optimizing treatment sequencing and managing toxicity. Future research should focus on refining patient selection criteria and exploring novel combination therapies to enhance efficacy and durability of response.	bladder
[Bladder cancer in geriatric patients].	Bladder cancer is one of the most commonly diagnosed cancers, especially in older people. Bladder cancer belongs to urothelial carcinomas, which can also occur in other parts of the urinary tract (also at the same time). The most common symptom of bladder cancer is hematuria. Bladder cancer treatment is largely based on surgery. Not all patients (due to comorbidities) will benefit from surgical treatment (especially in the case of radical cystectomy). Appropriate geriatric assessment of patients is crucial when qualifying for surgery. The aim of this article was to indicate the best management of a multimorbid geriatric patient with bladder cancer. The authors presented current knowledge and discussed interdisciplinary approach. The literature review included scientific articles that form the new standards and current guidelines of the European Association of Urology. Geriatric patients with bladder cancer require greater specialist involvement and multidisciplinary care. During qualification for treatment, close cooperation between urologist, oncologist, geriatrician, and other specialists is necessary. Due to the complex therapeutic process, not all patients will be able to follow all recommendations. Personalized medicine allows for the selection of the most appropriate therapeutic option. Further research is also needed on less invasive treatments, such as trimodal therapy, which includes transurethral resection of the bladder tumor, systemic chemotherapy, and external beam radiation therapy - especially for patients who are not eligible for radical treatment. Med Pr Work Health Saf. 2025;76(3):233-239.	bladder
End Points for the Next-Generation Bladder-Sparing Perioperative Trials for Patients With Muscle-Invasive Bladder Cancer.	PURPOSE: The evolving treatment landscape of muscle-invasive bladder cancer (MIBC) increasingly warrants novel trial design to evaluate perioperative strategies aimed at bladder preservation. To establish standardized outcome measures for evaluating organ preservation strategies in MIBC, the International Bladder Cancer Group (IBCG) and the Global Society of Rare Genitourinary Tumors (GSRGT) assembled an international, multidisciplinary consensus panel. METHODS: The IBCG and GSRGT gathered global bladder cancer experts and patient advocates to establish a framework for risk-adapted bladder-sparing treatment approaches for MIBC. Working groups reviewed the literature and developed draft recommendations, which were discussed at a live meeting in December 2024 in Milan. This was followed by voting by the members using a modified Delphi process. Recommendations achieving ≥75% agreement during the meeting were further refined and presented. RESULTS: Clinical complete response (cCR) definition should encompass the absence of high-grade malignancy on pathology and malignant cells on urine cytology and no evidence of local or metastatic disease on cross-sectional imaging. Although cCR remains immature as a primary or coprimary end point in registrational trials, it could serve as a suitable end point in early-phase studies and risk-adapted investigations. Event-free survival (EFS) remains the preferred primary end point as it could reliably capture the durability of clinically meaningful benefit after omittance of surgical consolidation or chemoradiation. Given the composite nature of EFS, events should be prespecified, evaluated in an intention-to-treat approach, and meticulously collected. Continuous assessment of individual patient preferences should begin at the outset of perioperative therapy discussions, with informed decision making prioritized throughout. CONCLUSION: The consensus definition of cCR and the framework presented in this study can serve as a foundation for thorough testing of risk-adapted bladder-sparing treatment paradigms for MIBC.	bladder
Circulating tumor DNA and urinary tumor DNA: useful biomarkers for bladder cancer detection.	INTRODUCTION: Bladder cancer (BC), a prevalent urinary system malignancy, presents challenges for early diagnosis because of its nonspecific symptoms and late-stage presentation, leading to poor prognosis. Liquid biopsy, particularly urine-based testing, has emerged as a promising noninvasive alternative to tissue biopsy for early cancer detection, monitoring, and treatment guidance. Urinary tumor DNA (utDNA) and circulating tumor DNA (ctDNA) are key biomarkers that offer direct, noninvasive access to urinary tract tumor genetic information. AREAS COVERED: This review explores key dimensions of ctDNA and utDNA in BC, including BC epidemiology and current diagnostic limitations; cfDNA detection technologies; applications, advantages, and roles of ctDNA and utDNA in recurrence monitoring, treatment response assessment, and prognostic stratification; and ongoing clinical trials. EXPERT OPINION: ctDNA and utDNA are transformative tools in BC management, offering real-time insights into tumor dynamics, treatment response, and prognosis. The short half-life of ctDNA enables rapid assessment of tumor burden changes, whereas the noninvasive collection of utDNA enhances patient compliance. Despite challenges such as low biomarker abundance in urine, heterogeneity, and standardization gaps, ongoing clinical trials have validated its clinical utility. Future integration of ctDNA/utDNA into clinical practice will enable personalized, noninvasive BC care, improving early diagnosis, treatment optimization, and patient outcomes.	bladder